Social deficits are characteristic of most major mental health disorders, including depression, bipolar disorder, schizophrenia, and autism. In many cases, social interactions that were once rewarding become aversive and individuals become withdrawn. Despite the negative impact that social withdrawal has on the individual and family, the mechanisms are unknown and treatments are lacking. The proposed research will fill this important gap by identifying neural mechanisms that naturally promote social interactions, which can be used to develop treatment options. The research turns to novel insights from the postpartum brain and applies them to non- parental adults. Nave prepartum female mice find social interactions with mouse pups to have low valence; however, postpartum females find social interactions with pups to be intensely rewarding. It is possible that the reward mechanisms altered in mothers may represent fundamental mechanisms that promote sociability across social contexts. Nuclear receptor subfamily 1, group D, member 1 (Nr1d1) (also known as Rev erb alpha) is of great interest because striking and reliable decreases in Nr1d1 expression occur in postpartum (i.e., prosocial) compared to prepartum mice in multiple brain regions regulating reward, including nucleus accumbens (NAC). Nr1d1 is a transcription factor involved in circadian rhythm regulation, but recent work suggests a key role for Nr1d1 in reward-related processes as well as disorders with social deficits, such as depression. Depression is associated with dysregulation of reward pathways and Nr1d1 may be the link between reward, social behavior, and depression. Recent work indicates that Nr1d1 in NAC interacts with and possibly regulates numerous reward-related genes. Still, the role of Nr1d1 in NAC in social reward is not known. The long- term goal is to understand the basis of changes in sociability with the possibility of opening avenues for devel- oping treatments to improve social deficits in humans. The objective here is to determine how decreases in Nr1d1 in NAC regulate social reward. Our central hypothesis is that decreases in Nr1d1 in NAC will improve social reward in a non-reproductive context. The rationale is that the findings will contribute key, missing information on the role of Nr1d1 in NAC on modulating social reward. In order to test the central hypothesis and accomplish the objective of the application, the following two specific aims are proposed. 1. Identify effects of decreasing Nr1d1 in NAC on social reward-related behaviors. 2. Identify effects of decreasing Nr1d1 in NAC on CNS processes using microarrays and bioinformatics approaches. Bioinformatics analysis will highlight pathways related to addiction/reward, mental health, neuronal activity, transcriptional regulation, and circadian rhythms. The approach is innovative as is the concept that Nr1d1 is a critical trigger for social reward. This work is significant because it will provide novel insights into new approaches on how to improve sociability. These studies will provide specific information about how Nr1d1 functions in adults to regulate social reward and could provide insights for understanding dysregulation in adults.